Oxazolidinones are compounds where an amine group and a hydroxyl group on adjacent carbon atoms have been cyclized to form a 5-membered ring containing a carbonyl group. Certain oxazolidinones have been shown to exhibit a variety of biological activities. For example, some oxazolidinones are inhibitors of monoamine oxidase-B, an enzyme implicated in Parkinson's disease. See, for example, Ding et al., J. Med. Chem. 36:3606-3610 (1993).
A a ten step synthesis of oxazolidinone antibiotics has been described. U.S. Pat. No. 5,547,950. A four step synthesis of the antibacterial compound U-100592 also has been reported. Schauss et al., Tetrahedron Letters, 37:7937-7940 (1996). A five step preparation of enantiomerically pure cis- and trans-N-(propionyl)hexahydrobenzoxazolidin-2-ones further was reported. De Parrodi et al., Tetrahedron: Asymmetry, 8:1075-1082 (1997).
Scientists have reported that certain oxazolidinone derivatives exhibit beneficial antibacterial effects. For instance, N-[3-[3-fluoro-4-(morpholin-4-yl)phenyl]2-oxooxazolidin-5(s)-ylmethyl]acet amide (below) has been reported to be useful for the treatment of bacterial infections. Lizondo et al., Drugs of the Future, 21:1116-1123 (1996). ##STR1##
The synthesis of the oxazolidinone antibacterial agent shown below has been reported. Wang et al., Tetrahedron, 45:1323-1326 (1989). This oxazolidinone was made using a process that included the reaction of an aniline with glycidol to provide an amino alcohol, and the diethylcarbonate mediated cyclization of the amino alcohol to afford an oxazolidinone. ##STR2##
The synthesis of oxazolidinone antibacterial agents, including the compound shown below has been reported. U.S. Pat. No. 4,705,799. The process used to make the compound shown below included a metal mediated reduction of a sulfonyl chloride to provide a sulfide. ##STR3##
The synthesis of oxazolidinone antibacterial agents, including the pyridyl compound shown below has been reported. U.S. Pat. No. 4,948,801. The process used included an organometallic mediated coupling of an organotin compound and an aryl iodide. ##STR4##
Synthetic routes to oxazolidinones often allow a chemist to produce only one compound at a time. These laborious methods can provide a limited number of compounds for evaluation in a biological screen. These methods cannot, however, provide the number of compounds required to supply a high-throughput biological screen, an assay technique whereby the activity of thousands of drug candidates, for example, per week, may be analyzed. This limitation on compound production is of practical importance since high-throughput screens are desirable and efficient for the discovery of new drugs.